HLA-B*0702 Cryptic Peptide Immunotherapy Optimization
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Solution Overview
Problem
Current cancer immunotherapy approaches targeting immunodominant peptides have shown disappointing results due to self-tolerance issues, while cryptic peptides, with low affinity for MHC I, are non-immunogenic and thus ineffective in inducing tumor immunity, particularly for HLA-B*0702 phenotype patients where few tumor peptides have been identified.
Innovation Solution
A method to enhance the immunogenicity of HLA-B*0702-restricted cryptic peptides by substituting the N-terminal residue with alanine or the C-terminal residue with leucine, increasing their affinity and immunogenicity, thereby inducing a specific CTL response against tumor cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunodominant peptides are targeted by tumor vaccines, then the immune system is stimulated, but self-tolerance prevents effective tumor immunity
Solution Approach 1:
Instead of targeting immunodominant peptides that are suppressed by self-tolerance, the invention inverts the approach by targeting cryptic peptides that are normally weakly presented but are not subject to self-tolerance. This inversion allows the vaccine to bypass the self-tolerance barrier while still inducing effective CTL responses against tumor antigens.
Solution Approach 2:
The invention changes the parameter of peptide selection from immunodominant to cryptic peptides. By selecting cryptic peptides with specific characteristics (low natural presentation but not subject to self-tolerance), the vaccine overcomes the self-tolerance limitation while maintaining the ability to induce strong CTL responses through optimized MHC binding.
2Object-affected harmful factors
If cryptic peptides are used for immunotherapy, then self-tolerance is avoided, but low MHC I affinity results in non-immunogenicity
Solution Approach 1:
The invention changes the binding affinity parameter of cryptic peptides by selecting and optimizing peptides with improved MHC I binding characteristics. This parameter optimization allows cryptic peptides to maintain their advantage of avoiding self-tolerance while gaining sufficient immunogenicity through enhanced MHC presentation.
Solution Approach 2:
The invention uses optimized MHC I molecules as intermediaries to present cryptic peptides effectively. By selecting cryptic peptides that can be optimally presented by MHC I, the system bridges the gap between avoiding self-tolerance and achieving sufficient immunogenicity for effective tumor immunity.
3Adaptability or versatility
If few HLA-B*0702 tumor peptides are identified, then patient-specific treatment is limited, but broader peptide selection increases complexity
Solution Approach 1:
The invention changes the selection parameters by focusing on cryptic peptides with specific MHC I binding characteristics rather than relying on traditional immunodominant peptide identification. This parameter shift enables the identification of effective peptides for HLA-B*0702 patients while maintaining a manageable selection process.
Data Source
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AI summary
The present invention relates to the field of peptide immunotherapy. In particular, the invention pertains to a method for identifying a HLA-B*0702-restricted cryptic epitope in an antigen, and to a method for increasing its immunogenicity. The invention also provides novel methods and materials for efficiently treating patients having an HLA- B*0702 phenotype.